Signet Ring Cell Carcinoma of the Urinary Bladder: Survival and Pathologic Outcomes from the National Cancer Database

Signet Ring Cell Carcinoma of the Urinary Bladder: Survival and Pathologic Outcomes from the National Cancer Database | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article Signet Ring Cell Carcinoma of the Urinary Bladder: Survival and Pathologic Outcomes from the National Cancer Database Deerush Kannan Sakthivel, Pushan Prabhakar, Mohamed Javid, Rohan Garje, and 1 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-7191166/v1 This work is licensed under a CC BY 4.0 License Status: Published Journal Publication published 13 Nov, 2025 Read the published version in International Urology and Nephrology → Version 1 posted You are reading this latest preprint version Abstract Purpose: Signet ring cell carcinoma (SRCC) of the urinary bladder is a rare and aggressive histologic variant with limited guidance on optimal treatment. This study aimed to characterize the clinicopathological features, treatment patterns, and survival outcomes of bladder SRCC using a large national dataset and to assess the impact of surgical and systemic therapies on prognosis. Methods: We queried the National Cancer Database (NCDB) for patients diagnosed with bladder SRCC between 2004 and 2018. Clinical and pathological staging, surgical approach (partial vs. radical cystectomy), chemotherapy use, and overall survival were analyzed. Kaplan–Meier survival curves and statistical comparisons were used to evaluate treatment outcomes. Results: A total of 60 patients with SRCC of the bladder were identified. A substantial proportion presented with advanced or unstaged disease (43.3% cTX, 38.4% pTX). Partial cystectomy was performed more often than radical cystectomy (56.7% vs. 31.6%). Chemotherapy was administered in 38.4% of patients, most commonly as multi-agent regimens. Median overall survival was approximately 30 months. No significant survival benefit was observed with chemotherapy administration. Conclusion: Bladder SRCC is associated with poor survival and considerable heterogeneity in staging and management. Our findings highlight the limited efficacy of systemic therapy and underscore the need for personalized, evidence-based treatment strategies. Signet ring cell carcinoma urinary bladder cancer National Cancer Database bladder cancer variants survival outcomes cystectomy Figures Figure 1 Figure 2 Figure 3 Introduction Bladder cancer is predominantly urothelial carcinoma, with adenocarcinomas accounting for only 0.5–2% of all primary bladder malignancies. [ 1 ] Among these, signet ring cell adenocarcinoma (SRCC) is an extremely rare and aggressive variant that accounts for 0.12–0.6% of all primary bladder malignancies. [ 2 ] Histologically, SRCC is defined by mucin-laden cells with peripherally displaced nuclei, with intracellular mucin comprising more than 50% of the tumour, unlike mucinous adenocarcinoma, which contains predominantly extracellular mucin. [ 3 ] While typically associated with gastric and colorectal cancers, bladder involvement is rare, with most cases resulting from direct invasion or metastatic spread via hematogenous or lymphatic routes. [ 4 ] SRCC is known for its poor prognosis, high metastatic potential, and resistance to conventional chemotherapy and radiotherapy. Most cases present as muscle-invasive disease, further contributing to poor survival outcomes.[ 5 ] This study utilizes the National Cancer Database (NCDB) to analyse one of the largest recent series of bladder SRCC cases. By incorporating real-world data from the past two decades, it aims to improve understanding of the tumours’ clinical presentation, diagnostic approach, treatment strategies, and survival outcomes, ultimately guiding more effective patient management. Materials and Methods This retrospective cohort study utilized data from the National Cancer Database (NCDB), a joint project of the American College of Surgeons and the American Cancer Society that captures approximately 70% of all newly diagnosed cancer cases in the United States. We identified patients diagnosed with SRCC of the urinary bladder between 2004–2020 using the International Classification of Diseases for Oncology, Third Edition (ICD-O-3) histology code in combination with primary site codes corresponding to the urinary bladder. Demographic variables including age, sex, race, insurance status, and comorbidities (as measured by the Charlson–Deyo comorbidity index) were extracted. Clinical and pathological staging information (T, N, and M categories), treatment modalities (surgery, chemotherapy, radiation), and survival data were obtained. Patients with incomplete essential data were excluded from outcome analysis as appropriate. Descriptive statistics were used to summarize patient characteristics and treatment patterns. Kaplan–Meier survival analysis was conducted to estimate overall survival (OS), defined as the time from diagnosis to death or last follow-up. All statistical analyses were performed using SPSS software (IBM Corp., Version 28.0). The study was exempt from Institutional Review Board (IRB) approval as it utilized de-identified, publicly available data. Results From an initial cohort of 1,291 patients with urachal carcinoma, 60 (4.6%) cases of signet ring cell histology were identified and included in the analysis. The majority were male (65%) and White (76.7%), with 33.3% aged below 50 years. Most patients received care at academic/research (33.3%) or integrated network cancer centres (30%). In terms of socioeconomic status, 38.3% belonged to the highest income quartile (≥ $ 74,063), and private insurance was the most common coverage (46.7%). A comorbidity score of 0 was recorded in 73.3% of patients as summarised in Table 1 . Table 1 Demographic variables in the study cohort Variable Signet Ring Cell Urachal Carcinoma Total n (%) 60 100 Age Less than 50 20 33.3 50–59 10 16.7 60–69 16 26.7 70–79 10 16.7 80 and above 4 6.7 Gender Male, n(%) 39 65 Female, n(%) 21 35 Race White, n(%) 46 76.7 Black, n(%) 7 11.7 Asian, n(%) 7 11.7 Facility Type Community, n(%) 3 5 Comprehensive Community, n(%) 11 18.3 Academic/ Research, n(%) 20 33.3 Integrated Network Cancer, n(%) 18 30 Unknown 8 13.3 Median Income = $ 74,063, n(%) 23 38.3 Missing, n(%) 2 3.3 Comorbidity Score 0, n(%) 44 73.3 1, n(%) 10 16.7 2 5 8.3 >=3 1 1.7 Clinical T staging was unavailable in 43.3%, with cT3 (18.4%) and cT2 (16.7%) being the most frequent among staged cases. Most patients were non-metastatic at diagnosis (cM0, 65%), while 13.3% had metastatic disease (cM1). Pathological staging showed pT3 in 36.9% and pTX in 38.4%. Surgical management was undertaken in 88.3% of patients, with partial cystectomy being the most common (56.7%). Chemotherapy was administered in 38.4%, primarily using multi-agent regimens (31.7%). The clinical characteristics are summarised in Table 2 . Table 2 Clinical presentation and treatment modality in the study cohort Clinical T Stage n % cTX 26 43.3 cT1 8 13.3 cT2 10 16.7 cT3 11 18.4 cT4 5 8.4 Clinical N Stage cNX 21 35 cN0 35 58.3 cN1 3 5 cN2 0 0 cN3 1 1.7 Clinical M Stage cMX 13 21.7 cM0 39 65 cM1 8 13.3 Pathological T Stage pTX 23 38.4 pT1 1 1.7 pT2 9 14.9 pT3 22 36.9 pT4 5 8.3 Pathological N Stage pNX 32 53.4 pN0 22 36.7 pN1 4 6.7 pN2 2 3.3 Surgery No surgery 7 11.7 Local excision 3 5 Partial cystectomy 34 56.7 Radical cystectomy 5 8.3 Unknown surgery 11 18.3 Chemotherapy No chemotherapy 34 56.7 Chemotherapy given, type unknown 1 1.7 Single agent 3 5 Multi agent 19 31.7 Unknown 3 5 The Kaplan–Meier survival analysis demonstrated poor overall survival among patients with signet ring cell urachal carcinoma. The median overall survival was approximately 30 months. At 5 years (60 months), the estimated survival probability was less than 25%, and long-term survival beyond 10 years was observed in a small subset of patients. The curve showed a steep decline within the first 2 years from diagnosis, reflecting the aggressive nature of the disease. Several patients were censored beyond 100 months, indicating prolonged survival in a limited number of cases. Survival comparisons were made between patients who underwent partial versus radical cystectomy, those who received chemotherapy versus those who did not, and between patients with SRCC and other histological subtypes of urachal carcinoma. (Figs. 1 – 3 ) The median overall survival for urachal adenocarcinoma is 78.980 months The median overall survival for signet ring urachal carcinoma is 29.570 months (p < 0.001) The median overall survival for patients with no chemotherapy is 36.010 months The median overall survival for patients with chemotherapy is 21.220 months (p-value 0.397) The median overall survival for partial cystectomy is 58.51 months The median overall survival for radical cystectomy is 23.79 months (p-value 0.007) Discussion SRCC of the bladder represents a rare and aggressive histologic variant, with limited data available to guide its optimal management. The diagnostic and therapeutic challenges associated with this entity are compounded by the absence of large prospective studies. Consequently, current understanding is primarily derived from case reports and small institutional series, thereby limiting the robustness of available evidence. [ 6 , 7 ] Utilizing data from the NCDB, the present study seeks to characterize the clinicopathological features, treatment patterns, and oncologic outcomes of SRCC, with an emphasis on its distinct biological behaviour. Although prior literature has explored variant histologies in bladder cancer, very few studies have focused exclusively on SRCC, highlighting the need for greater awareness and disease-specific strategies for this uncommon subtype. Our analysis corroborates the aggressive clinical nature of bladder SRCC. A substantial proportion of patients presented with advanced-stage disease or incomplete clinical staging, with clinical T stage unreported in 43.3% of cases. Among those staged, cT3 and cT2 comprised 18.4% and 16.7%, respectively. Although the majority of patients were non-metastatic at diagnosis (cM0 in 65%), a notable subset (13.3%) had evidence of metastatic disease, and a steep decline in survival during the first two years post-diagnosis reflects the rapidly progressive course characteristic of this histology. On pathological evaluation, locally advanced tumors (pT3) were observed in 36.9% of cases, while 38.4% remained unstaged (pTX), further underscoring diagnostic variability and potential gaps in care pathways. Approximately 25% of patients present with distant metastasis, and around 50% have locally advanced disease at the time of diagnosis, as reported in the review by Wang et al. This pattern has remained consistent over the decades, with no significant improvement in outcomes. [ 8 ] Surgical management was employed in 88.3% of patients, with a disproportionately high rate of partial cystectomy (56.7%). This finding may reflect diagnostic uncertainty, patient preference, or lack of consensus regarding the role of radical cystectomy in this variant. The high rate of unstaged disease could also be attributable to the increased use of partial cystectomy, which may limit comprehensive pathological evaluation. Chemotherapy utilization was modest (38.4%), with multi-agent regimens administered in 31.7% of patients, despite existing evidence advocating multimodal approaches in aggressive bladder cancer subtypes. The variability in outcomes and management of the disease, as well as the need for further prospective studies to develop personalized treatment approaches, have already been reported in a large population-based analysis. [ 9 ] There remains a paucity of data guiding systemic therapy for SRCC of the bladder. Chemotherapy regimens are often extrapolated from those used in conventional urothelial carcinoma, with limited data on efficacy in SRCC specifically. Concerns persist regarding the potential for neoadjuvant chemotherapy to delay definitive surgical management in the absence of proven benefit, potentially compromising oncologic outcomes. Similarly, the role of radiation therapy remains ill-defined; although some prior literature suggests potential utility, none of the patients in this cohort received radiotherapy—potentially reflecting both the lack of supporting evidence and its limited applicability in surgically fit patients. The variability in chemotherapy use, regimens, and outcomes has been extensively analyzed, with reports showing considerable variation in the literature. [ 10 , 11 ] Kaplan–Meier survival analysis highlights the poor prognosis associated with bladder SRCC, with a median overall survival of approximately 30 months and fewer than 25% of patients alive at five years. A small subset demonstrated extended survival beyond 100 months, suggesting that durable outcomes may be achievable in select patients with timely and aggressive intervention. Survival was significantly worse (p < 0.05) in patients with SRCC compared to those with non-SRCC urachal carcinomas, supporting the inherently aggressive nature of this histologic variant. Interestingly, patients who underwent partial cystectomy experienced superior survival compared to those who underwent radical cystectomy. Although this may reflect selection bias, further investigation may help identify a subset of patients who could benefit from bladder-preserving approaches, thereby avoiding the morbidity associated with urinary diversion. Moreover, the administration of chemotherapy did not confer a significant survival advantage, emphasizing the uncertain role of systemic therapy in this setting. Several studies have confirmed the aggressive nature of bladder SRCC, with poor overall survival despite conventional treatments. [ 12 , 13 ] The high rate of partial cystectomy observed in this cohort raises important clinical considerations regarding the balance between oncologic control and quality of life. In a disease characterized by poor survival, prioritizing bladder preservation may be appropriate in selected cases. However, radical cystectomy may offer improved local control and potentially reduce recurrence risk. [ 11 ] Therefore, treatment decisions should be individualized, incorporating tumor stage, patient age, comorbidities, and performance status. This study underscores significant variability in staging, presentation, and treatment patterns in bladder SRCC, reflective of the absence of standardized clinical pathways. Nevertheless, reporting outcomes from this rare cohort is essential to enhance the current understanding of SRCC and inform clinical practice. The principal challenges remain the aggressive nature of the disease and the scarcity of cases, which hinder prospective data collection. In the absence of randomized data, a personalized approach to treatment, along with comprehensive documentation of clinical, pathological, and quality-of-life parameters, may serve as a platform for generating future hypotheses and guiding therapeutic strategies. Limitations of this study include its retrospective design and reliance on the NCDB, which lacks detail on chemotherapy regimens, patient performance status, and quality-of-life metrics. The high proportion of missing staging data may impact the interpretation of results. Additionally, the rarity of SRCC limits the power of subgroup analyses and the generalizability of findings. Conclusion SRCC of the bladder remains a challenging entity with aggressive behaviour and limited evidence-based treatment guidelines. Our NCDB analysis reveals significant heterogeneity in staging and management, with no clear survival benefit from chemotherapy. Continued reporting and collaborative efforts are essential to guide future management. Declarations Conflict of interest – Nil No funding was received to conduct this study Author Contribution •Study concept and design: Deerush Kannan Sakthivel, Manoharan Murugesan•Data acquisition: Deerush Kannan Sakthivel, Pushan Prabakar•Data analysis: Deerush Kannan Sakthivel, Pushan Prabakar, Mohamed Javid•Drafting of the manuscript: Deerush Kannan Sakthivel, Pushan Prabakar, Mohamed Javid •Critical revision of the manuscript: Deerush Kannan Sakthivel, Manoharan Murugesan, Rohan Garje References Grignon DJ, Ro JY, Ayala AG, et al. Primary signet-ring cell carcinoma of the urinary bladder. Am J Clin Pathol. 1991;95:13–20. doi: 10.1093/ajcp/95.1.13 . Lendorf ME, Dohn LH, Dunga BA, Loya AC, Pappot H. An updated review on primary signet-ring cell carcinoma of the urinary bladder and report of a case. Scand J Urol. 2018;52(2):87–93. doi: 10.1080/21681805.2017.1418020 . WHO. Digestive System Tumours, WHO Classification of Tumours Series. 5th ed. International Agency for Research on Cancer; Lyon, France: 2019. Benesch MGK, Mathieson A. Epidemiology of Signet Ring Cell Adenocarcinomas. Cancers (Basel). 2020;12(6):1544. Published 2020 Jun 11. doi: 10.3390/cancers12061544 Alradhi M, Safi M, Tao S, et al. Surgery improves survival in bladder signet-ring cell carcinoma-a population-based study. Ther Adv Urol. 2022;14:17562872221079473. Published 2022 Apr 7. doi: 10.1177/17562872221079473 Benerjee N, Parmar K, Vaiphei K. Primary signet-ring cell carcinoma of the urinary bladder. Autops Case Rep. 2021;11:e2021264. Published 2021 Apr 22. doi: 10.4322/acr.2021.264 Boukettaya W, Feki J, Charfi S, et al. Primary Signet Ring Cell Adenocarcinoma of the Urinary Bladder: A Report of 2 Cases. Urol Case Rep. 2014;2(3):85–87. Published 2014 Apr 8. doi: 10.1016/j.eucr.2014.03.004 Wang J, Wang FW. Clinical characteristics and outcomes of patients with primary signet-ring cell carcinoma of the urinary bladder. Urol Int. 2011;86(4):453–460. doi: 10.1159/000324263 Xie Y, Zhang Y, Du Z, et al. Treatment Options for Signet Ring Cell Carcinoma of the Urinary Bladder: A Population-Based Study. Cancer Control. 2024;31:10732748241278485. doi: 10.1177/10732748241278485 von der Maase H, Hansen SW, Roberts JT, et al. Gemcitabine and cisplatin versus methotrexate, vinblastine, doxorubicin, and cisplatin in advanced or metastatic bladder cancer: results of a large, randomized, multinational, multicenter, phase III study. J Clin Oncol. 2000;18(17):3068–3077. doi: 10.1200/JCO.2000.18.17.3068 Hirano Y, Suzuki K, Fujita K, et al. Primary signet ring cell carcinoma of the urinary bladder successfully treated with intra-arterial chemotherapy alone. Urology. 2002;59(4):601. doi: 10.1016/s0090-4295(01)01676-4 Ma T, Wang X, Tian Z, et al. Nomograms to predict individual prognosis of patients with primary signet ring cell carcinoma of the urinary bladder. Transl Cancer Res. 2021;10(9):3948–3962. doi: 10.21037/tcr-21-929 Jayarajah U, Fernando DMH, Herath KB, de Silva MVC, Goonewardena SAS. Primary Signet-Ring Cell Adenocarcinoma of the Urinary Bladder Treated with Partial Cystectomy: A Case Report and Review of the Literature. Case Rep Urol. 2017;2017:6829692. doi: 10.1155/2017/6829692 Additional Declarations No competing interests reported. Cite Share Download PDF Status: Published Journal Publication published 13 Nov, 2025 Read the published version in International Urology and Nephrology → Version 1 posted You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-7191166","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":493203192,"identity":"4637df6a-60c7-423d-bf42-2edbbd391e8f","order_by":0,"name":"Deerush Kannan 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Florida","correspondingAuthor":false,"prefix":"","firstName":"Murugesan","middleName":"","lastName":"Manoharan","suffix":""}],"badges":[],"createdAt":"2025-07-23 02:08:13","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-7191166/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-7191166/v1","draftVersion":[],"editorialEvents":[{"content":"https://doi.org/10.1007/s11255-025-04906-3","type":"published","date":"2025-11-13T15:58:27+00:00"}],"editorialNote":"","failedWorkflow":false,"files":[{"id":88094262,"identity":"4374e4a5-e7d2-40ae-b2cd-7892f2293bd5","added_by":"auto","created_at":"2025-08-01 10:47:42","extension":"jpeg","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":31371,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eComparative survival analysis between signet ring cell carcinoma and non–signet ring urachal carcinomas.\u003c/strong\u003e\u003c/p\u003e","description":"","filename":"floatimage1.jpeg","url":"https://assets-eu.researchsquare.com/files/rs-7191166/v1/2cad0b980e51a0ea7e401105.jpeg"},{"id":88095973,"identity":"387bae90-bcc2-463b-b373-c68628177e83","added_by":"auto","created_at":"2025-08-01 10:55:42","extension":"jpeg","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":189685,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eComparative survival analysis between signet ring cell carcinoma patients who received chemotherapy and those who did not.\u003c/strong\u003e\u003c/p\u003e","description":"","filename":"floatimage2.jpeg","url":"https://assets-eu.researchsquare.com/files/rs-7191166/v1/0b542eed7f54ac1d0b16f3e6.jpeg"},{"id":88094268,"identity":"535e6c9e-f1d3-4ff5-b0db-39c5e8261b8f","added_by":"auto","created_at":"2025-08-01 10:47:42","extension":"jpeg","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":29058,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eComparative survival analysis between signet ring cell carcinoma patients who underwent radical cystectomy and those who underwent partial cystectomy.\u003c/strong\u003e\u003c/p\u003e","description":"","filename":"floatimage3.jpeg","url":"https://assets-eu.researchsquare.com/files/rs-7191166/v1/37cc4275bbcbe10c609ca659.jpeg"},{"id":96105117,"identity":"c58f0f8c-1177-4c56-baec-0dda3daa8023","added_by":"auto","created_at":"2025-11-17 16:08:52","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":1001615,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-7191166/v1/ca2b929d-6964-4dcb-bd7a-d2cedde0ffb4.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Signet Ring Cell Carcinoma of the Urinary Bladder: Survival and Pathologic Outcomes from the National Cancer Database","fulltext":[{"header":"Introduction","content":"\u003cp\u003eBladder cancer is predominantly urothelial carcinoma, with adenocarcinomas accounting for only 0.5\u0026ndash;2% of all primary bladder malignancies. [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e] Among these, signet ring cell adenocarcinoma (SRCC) is an extremely rare and aggressive variant that accounts for 0.12\u0026ndash;0.6% of all primary bladder malignancies. [\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e] Histologically, SRCC is defined by mucin-laden cells with peripherally displaced nuclei, with intracellular mucin comprising more than 50% of the tumour, unlike mucinous adenocarcinoma, which contains predominantly extracellular mucin. [\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e] While typically associated with gastric and colorectal cancers, bladder involvement is rare, with most cases resulting from direct invasion or metastatic spread via hematogenous or lymphatic routes. [\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e]\u003c/p\u003e\u003cp\u003eSRCC is known for its poor prognosis, high metastatic potential, and resistance to conventional chemotherapy and radiotherapy. Most cases present as muscle-invasive disease, further contributing to poor survival outcomes.[\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e]\u003c/p\u003e\u003cp\u003eThis study utilizes the National Cancer Database (NCDB) to analyse one of the largest recent series of bladder SRCC cases. By incorporating real-world data from the past two decades, it aims to improve understanding of the tumours\u0026rsquo; clinical presentation, diagnostic approach, treatment strategies, and survival outcomes, ultimately guiding more effective patient management.\u003c/p\u003e"},{"header":"Materials and Methods","content":"\u003cp\u003eThis retrospective cohort study utilized data from the National Cancer Database (NCDB), a joint project of the American College of Surgeons and the American Cancer Society that captures approximately 70% of all newly diagnosed cancer cases in the United States. We identified patients diagnosed with SRCC of the urinary bladder between 2004\u0026ndash;2020 using the International Classification of Diseases for Oncology, Third Edition (ICD-O-3) histology code in combination with primary site codes corresponding to the urinary bladder.\u003c/p\u003e\u003cp\u003eDemographic variables including age, sex, race, insurance status, and comorbidities (as measured by the Charlson\u0026ndash;Deyo comorbidity index) were extracted. Clinical and pathological staging information (T, N, and M categories), treatment modalities (surgery, chemotherapy, radiation), and survival data were obtained. Patients with incomplete essential data were excluded from outcome analysis as appropriate.\u003c/p\u003e\u003cp\u003eDescriptive statistics were used to summarize patient characteristics and treatment patterns. Kaplan\u0026ndash;Meier survival analysis was conducted to estimate overall survival (OS), defined as the time from diagnosis to death or last follow-up. All statistical analyses were performed using SPSS software (IBM Corp., Version 28.0). The study was exempt from Institutional Review Board (IRB) approval as it utilized de-identified, publicly available data.\u003c/p\u003e"},{"header":"Results","content":"\u003cp\u003eFrom an initial cohort of 1,291 patients with urachal carcinoma, 60 (4.6%) cases of signet ring cell histology were identified and included in the analysis. The majority were male (65%) and White (76.7%), with 33.3% aged below 50 years. Most patients received care at academic/research (33.3%) or integrated network cancer centres (30%). In terms of socioeconomic status, 38.3% belonged to the highest income quartile (\u0026ge;\u003cspan\u003e$\u003c/span\u003e74,063), and private insurance was the most common coverage (46.7%). A comorbidity score of 0 was recorded in 73.3% of patients as summarised in Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e.\u003c/p\u003e\u003cp\u003e\u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab1\" border=\"1\"\u003e\u003ccaption language=\"En\"\u003e\u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e\u003cdiv class=\"CaptionContent\"\u003e\u003cp\u003eDemographic variables in the study cohort\u003c/p\u003e\u003c/div\u003e\u003c/caption\u003e\u003ccolgroup cols=\"3\"\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e\u003cthead\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c1\"\u003e\u003cp\u003eVariable\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colspan=\"2\" nameend=\"c3\" namest=\"c2\"\u003e\u003cp\u003eSignet Ring Cell Urachal Carcinoma\u003c/p\u003e\u003c/th\u003e\u003c/tr\u003e\u003c/thead\u003e\u003ctbody\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eTotal n (%)\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e60\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e100\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eAge\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eLess than 50\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e20\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e33.3\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e50\u0026ndash;59\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e10\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e16.7\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e60\u0026ndash;69\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e16\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e26.7\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e70\u0026ndash;79\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e10\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e16.7\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e80 and above\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e4\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e6.7\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eGender\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eMale, n(%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e39\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e65\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eFemale, n(%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e21\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e35\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eRace\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eWhite, n(%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e46\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e76.7\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eBlack, n(%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e7\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e11.7\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eAsian, n(%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e7\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e11.7\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eFacility Type\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eCommunity, n(%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e3\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e5\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eComprehensive Community, n(%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e11\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e18.3\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eAcademic/ Research, n(%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e20\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e33.3\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eIntegrated Network Cancer, n(%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e18\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e30\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eUnknown\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e8\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e13.3\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eMedian Income\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u0026lt;\u003cspan\u003e$\u003c/span\u003e46,277, n (%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e11\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e18.3\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cspan\u003e$\u003c/span\u003e46,278-\u003cspan\u003e$\u003c/span\u003e57,856, n(%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e12\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e20\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cspan\u003e$\u003c/span\u003e57,857\u0026thinsp;\u0026minus;\u0026thinsp;74,062, n(%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e12\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e20\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u0026gt;=\u003cspan\u003e$\u003c/span\u003e74,063, n(%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e23\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e38.3\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eMissing, n(%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e2\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e3.3\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eComorbidity Score\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e0, n(%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e44\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e73.3\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e1, n(%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e10\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e16.7\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e2\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e5\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e8.3\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u0026gt;=3\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e1\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e1.7\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003c/tbody\u003e\u003c/colgroup\u003e\u003c/table\u003e\u003c/div\u003e\u003c/p\u003e\u003cp\u003eClinical T staging was unavailable in 43.3%, with cT3 (18.4%) and cT2 (16.7%) being the most frequent among staged cases. Most patients were non-metastatic at diagnosis (cM0, 65%), while 13.3% had metastatic disease (cM1). Pathological staging showed pT3 in 36.9% and pTX in 38.4%.\u003c/p\u003e\u003cp\u003eSurgical management was undertaken in 88.3% of patients, with partial cystectomy being the most common (56.7%). Chemotherapy was administered in 38.4%, primarily using multi-agent regimens (31.7%). The clinical characteristics are summarised in Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e.\u003c/p\u003e\u003cp\u003e\u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab2\" border=\"1\"\u003e\u003ccaption language=\"En\"\u003e\u003cdiv class=\"CaptionNumber\"\u003eTable 2\u003c/div\u003e\u003cdiv class=\"CaptionContent\"\u003e\u003cp\u003eClinical presentation and treatment modality in the study cohort\u003c/p\u003e\u003c/div\u003e\u003c/caption\u003e\u003ccolgroup cols=\"3\"\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e\u003cthead\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c1\"\u003e\u003cp\u003eClinical T Stage\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c2\"\u003e\u003cp\u003en\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c3\"\u003e\u003cp\u003e%\u003c/p\u003e\u003c/th\u003e\u003c/tr\u003e\u003c/thead\u003e\u003ctbody\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003ecTX\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e26\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e43.3\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003ecT1\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e8\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e13.3\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003ecT2\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e10\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e16.7\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003ecT3\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e11\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e18.4\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003ecT4\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e5\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e8.4\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eClinical N Stage\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003ecNX\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e21\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e35\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003ecN0\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e35\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e58.3\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003ecN1\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e3\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e5\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003ecN2\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e0\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e0\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003ecN3\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e1\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e1.7\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eClinical M Stage\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003ecMX\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e13\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e21.7\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003ecM0\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e39\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e65\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003ecM1\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e8\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e13.3\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003ePathological T Stage\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003epTX\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e23\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e38.4\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003epT1\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e1\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e1.7\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003epT2\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e9\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e14.9\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003epT3\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e22\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e36.9\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003epT4\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e5\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e8.3\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003ePathological N Stage\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003epNX\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e32\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e53.4\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003epN0\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e22\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e36.7\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003epN1\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e4\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e6.7\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003epN2\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e2\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e3.3\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eSurgery\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eNo surgery\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e7\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e11.7\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eLocal excision\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e3\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e5\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003ePartial cystectomy\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e34\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e56.7\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eRadical cystectomy\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e5\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e8.3\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eUnknown surgery\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e11\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e18.3\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eChemotherapy\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eNo chemotherapy\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e34\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e56.7\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eChemotherapy given, type unknown\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e1\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e1.7\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eSingle agent\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e3\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e5\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eMulti agent\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e19\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e31.7\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eUnknown\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e3\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e5\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003c/tbody\u003e\u003c/colgroup\u003e\u003c/table\u003e\u003c/div\u003e\u003c/p\u003e\u003cp\u003eThe Kaplan\u0026ndash;Meier survival analysis demonstrated poor overall survival among patients with signet ring cell urachal carcinoma. The median overall survival was approximately 30 months. At 5 years (60 months), the estimated survival probability was less than 25%, and long-term survival beyond 10 years was observed in a small subset of patients. The curve showed a steep decline within the first 2 years from diagnosis, reflecting the aggressive nature of the disease. Several patients were censored beyond 100 months, indicating prolonged survival in a limited number of cases. Survival comparisons were made between patients who underwent partial versus radical cystectomy, those who received chemotherapy versus those who did not, and between patients with SRCC and other histological subtypes of urachal carcinoma. (Figs.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e\u0026ndash;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003e)\u003c/p\u003e\u003cp\u003e\u003c/p\u003e\u003cp\u003eThe median overall survival for urachal adenocarcinoma is 78.980 months\u003c/p\u003e\u003cp\u003eThe median overall survival for signet ring urachal carcinoma is 29.570 months (p\u0026thinsp;\u0026lt;\u0026thinsp;0.001)\u003c/p\u003e\u003cp\u003e\u003c/p\u003e\u003cp\u003eThe median overall survival for patients with no chemotherapy is 36.010 months\u003c/p\u003e\u003cp\u003eThe median overall survival for patients with chemotherapy is 21.220 months (p-value 0.397)\u003c/p\u003e\u003cp\u003e\u003c/p\u003e\u003cp\u003eThe median overall survival for partial cystectomy is 58.51 months\u003c/p\u003e\u003cp\u003eThe median overall survival for radical cystectomy is 23.79 months (p-value 0.007)\u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eSRCC of the bladder represents a rare and aggressive histologic variant, with limited data available to guide its optimal management. The diagnostic and therapeutic challenges associated with this entity are compounded by the absence of large prospective studies. Consequently, current understanding is primarily derived from case reports and small institutional series, thereby limiting the robustness of available evidence. [\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e, \u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e] Utilizing data from the NCDB, the present study seeks to characterize the clinicopathological features, treatment patterns, and oncologic outcomes of SRCC, with an emphasis on its distinct biological behaviour. Although prior literature has explored variant histologies in bladder cancer, very few studies have focused exclusively on SRCC, highlighting the need for greater awareness and disease-specific strategies for this uncommon subtype.\u003c/p\u003e\u003cp\u003eOur analysis corroborates the aggressive clinical nature of bladder SRCC. A substantial proportion of patients presented with advanced-stage disease or incomplete clinical staging, with clinical T stage unreported in 43.3% of cases. Among those staged, cT3 and cT2 comprised 18.4% and 16.7%, respectively. Although the majority of patients were non-metastatic at diagnosis (cM0 in 65%), a notable subset (13.3%) had evidence of metastatic disease, and a steep decline in survival during the first two years post-diagnosis reflects the rapidly progressive course characteristic of this histology. On pathological evaluation, locally advanced tumors (pT3) were observed in 36.9% of cases, while 38.4% remained unstaged (pTX), further underscoring diagnostic variability and potential gaps in care pathways. Approximately 25% of patients present with distant metastasis, and around 50% have locally advanced disease at the time of diagnosis, as reported in the review by Wang et al. This pattern has remained consistent over the decades, with no significant improvement in outcomes. [\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e]\u003c/p\u003e\u003cp\u003eSurgical management was employed in 88.3% of patients, with a disproportionately high rate of partial cystectomy (56.7%). This finding may reflect diagnostic uncertainty, patient preference, or lack of consensus regarding the role of radical cystectomy in this variant. The high rate of unstaged disease could also be attributable to the increased use of partial cystectomy, which may limit comprehensive pathological evaluation. Chemotherapy utilization was modest (38.4%), with multi-agent regimens administered in 31.7% of patients, despite existing evidence advocating multimodal approaches in aggressive bladder cancer subtypes. The variability in outcomes and management of the disease, as well as the need for further prospective studies to develop personalized treatment approaches, have already been reported in a large population-based analysis. [\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e]\u003c/p\u003e\u003cp\u003eThere remains a paucity of data guiding systemic therapy for SRCC of the bladder. Chemotherapy regimens are often extrapolated from those used in conventional urothelial carcinoma, with limited data on efficacy in SRCC specifically. Concerns persist regarding the potential for neoadjuvant chemotherapy to delay definitive surgical management in the absence of proven benefit, potentially compromising oncologic outcomes. Similarly, the role of radiation therapy remains ill-defined; although some prior literature suggests potential utility, none of the patients in this cohort received radiotherapy\u0026mdash;potentially reflecting both the lack of supporting evidence and its limited applicability in surgically fit patients. The variability in chemotherapy use, regimens, and outcomes has been extensively analyzed, with reports showing considerable variation in the literature. [\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e, \u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e]\u003c/p\u003e\u003cp\u003eKaplan\u0026ndash;Meier survival analysis highlights the poor prognosis associated with bladder SRCC, with a median overall survival of approximately 30 months and fewer than 25% of patients alive at five years. A small subset demonstrated extended survival beyond 100 months, suggesting that durable outcomes may be achievable in select patients with timely and aggressive intervention. Survival was significantly worse (p\u0026thinsp;\u0026lt;\u0026thinsp;0.05) in patients with SRCC compared to those with non-SRCC urachal carcinomas, supporting the inherently aggressive nature of this histologic variant. Interestingly, patients who underwent partial cystectomy experienced superior survival compared to those who underwent radical cystectomy. Although this may reflect selection bias, further investigation may help identify a subset of patients who could benefit from bladder-preserving approaches, thereby avoiding the morbidity associated with urinary diversion. Moreover, the administration of chemotherapy did not confer a significant survival advantage, emphasizing the uncertain role of systemic therapy in this setting. Several studies have confirmed the aggressive nature of bladder SRCC, with poor overall survival despite conventional treatments. [\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e, \u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e]\u003c/p\u003e\u003cp\u003eThe high rate of partial cystectomy observed in this cohort raises important clinical considerations regarding the balance between oncologic control and quality of life. In a disease characterized by poor survival, prioritizing bladder preservation may be appropriate in selected cases. However, radical cystectomy may offer improved local control and potentially reduce recurrence risk. [\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e] Therefore, treatment decisions should be individualized, incorporating tumor stage, patient age, comorbidities, and performance status.\u003c/p\u003e\u003cp\u003eThis study underscores significant variability in staging, presentation, and treatment patterns in bladder SRCC, reflective of the absence of standardized clinical pathways. Nevertheless, reporting outcomes from this rare cohort is essential to enhance the current understanding of SRCC and inform clinical practice. The principal challenges remain the aggressive nature of the disease and the scarcity of cases, which hinder prospective data collection. In the absence of randomized data, a personalized approach to treatment, along with comprehensive documentation of clinical, pathological, and quality-of-life parameters, may serve as a platform for generating future hypotheses and guiding therapeutic strategies.\u003c/p\u003e\u003cp\u003eLimitations of this study include its retrospective design and reliance on the NCDB, which lacks detail on chemotherapy regimens, patient performance status, and quality-of-life metrics. The high proportion of missing staging data may impact the interpretation of results. Additionally, the rarity of SRCC limits the power of subgroup analyses and the generalizability of findings.\u003c/p\u003e"},{"header":"Conclusion","content":"\u003cp\u003eSRCC of the bladder remains a challenging entity with aggressive behaviour and limited evidence-based treatment guidelines. Our NCDB analysis reveals significant heterogeneity in staging and management, with no clear survival benefit from chemotherapy. Continued reporting and collaborative efforts are essential to guide future management.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003eConflict of interest – Nil\u003c/p\u003e\n\u003cp\u003eNo funding was received to conduct this study\u003c/p\u003e\u003ch2\u003eAuthor Contribution\u003c/h2\u003e\u003cp\u003e\u0026bull;Study concept and design: Deerush Kannan Sakthivel, Manoharan Murugesan\u0026bull;Data acquisition: Deerush Kannan Sakthivel, Pushan Prabakar\u0026bull;Data analysis: Deerush Kannan Sakthivel, Pushan Prabakar, Mohamed Javid\u0026bull;Drafting of the manuscript: Deerush Kannan Sakthivel, Pushan Prabakar, Mohamed Javid \u0026bull;Critical revision of the manuscript: Deerush Kannan Sakthivel, Manoharan Murugesan, Rohan Garje\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eGrignon DJ, Ro JY, Ayala AG, et al. Primary signet-ring cell carcinoma of the urinary bladder. 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Nomograms to predict individual prognosis of patients with primary signet ring cell carcinoma of the urinary bladder. Transl Cancer Res. 2021;10(9):3948\u0026ndash;3962. doi:\u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.21037/tcr-21-929\u003c/span\u003e\u003cspan address=\"10.21037/tcr-21-929\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eJayarajah U, Fernando DMH, Herath KB, de Silva MVC, Goonewardena SAS. Primary Signet-Ring Cell Adenocarcinoma of the Urinary Bladder Treated with Partial Cystectomy: A Case Report and Review of the Literature. Case Rep Urol. 2017;2017:6829692. doi:\u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1155/2017/6829692\u003c/span\u003e\u003cspan address=\"10.1155/2017/6829692\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":true,"highlight":"","institution":"","isAcceptedByJournal":true,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"Signet ring cell carcinoma, urinary bladder cancer, National Cancer Database, bladder cancer variants, survival outcomes, cystectomy","lastPublishedDoi":"10.21203/rs.3.rs-7191166/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-7191166/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003ePurpose:\u003c/h2\u003e\u003cp\u003eSignet ring cell carcinoma (SRCC) of the urinary bladder is a rare and aggressive histologic variant with limited guidance on optimal treatment. This study aimed to characterize the clinicopathological features, treatment patterns, and survival outcomes of bladder SRCC using a large national dataset and to assess the impact of surgical and systemic therapies on prognosis.\u003c/p\u003e\u003ch2\u003eMethods:\u003c/h2\u003e\u003cp\u003eWe queried the National Cancer Database (NCDB) for patients diagnosed with bladder SRCC between 2004 and 2018. Clinical and pathological staging, surgical approach (partial vs. radical cystectomy), chemotherapy use, and overall survival were analyzed. Kaplan\u0026ndash;Meier survival curves and statistical comparisons were used to evaluate treatment outcomes.\u003c/p\u003e\u003ch2\u003eResults:\u003c/h2\u003e\u003cp\u003eA total of 60 patients with SRCC of the bladder were identified. A substantial proportion presented with advanced or unstaged disease (43.3% cTX, 38.4% pTX). Partial cystectomy was performed more often than radical cystectomy (56.7% vs. 31.6%). Chemotherapy was administered in 38.4% of patients, most commonly as multi-agent regimens. Median overall survival was approximately 30 months. No significant survival benefit was observed with chemotherapy administration.\u003c/p\u003e\u003ch2\u003eConclusion:\u003c/h2\u003e\u003cp\u003eBladder SRCC is associated with poor survival and considerable heterogeneity in staging and management. Our findings highlight the limited efficacy of systemic therapy and underscore the need for personalized, evidence-based treatment strategies.\u003c/p\u003e","manuscriptTitle":"Signet Ring Cell Carcinoma of the Urinary Bladder: Survival and Pathologic Outcomes from the National Cancer Database","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-08-01 10:47:37","doi":"10.21203/rs.3.rs-7191166/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"29783f75-e254-4466-81ee-af0baa1d14c9","owner":[],"postedDate":"August 1st, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2025-11-17T16:03:37+00:00","versionOfRecord":{"articleIdentity":"rs-7191166","link":"https://doi.org/10.1007/s11255-025-04906-3","journal":{"identity":"international-urology-and-nephrology","isVorOnly":false,"title":"International Urology and Nephrology"},"publishedOn":"2025-11-13 15:58:27","publishedOnDateReadable":"November 13th, 2025"},"versionCreatedAt":"2025-08-01 10:47:37","video":"","vorDoi":"10.1007/s11255-025-04906-3","vorDoiUrl":"https://doi.org/10.1007/s11255-025-04906-3","workflowStages":[]},"version":"v1","identity":"rs-7191166","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-7191166","identity":"rs-7191166","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}